This invention relates to the treatment of Acne Vulgaris (hereinafter sometimes referred to as "acne").
Acne is recognized as an inflammatory disease, very common at puberty, occurring in skin areas where sebaceous glands are largest and most active. There are a number of pathological processes which lead to the manifestation of acne. Changes occur in the quality and/or quantity of the sebum, an oily secretion produced by the sebaceous glands. These changes are associated with alterations in the secretory cells, in the sebaceous glands, and in the surrounding connective tissue elements. In areas of actual or potential hair growth, abnormalities of the hair follicles and hair may be associated with the disturbances in the sebaceous glands which are located in the immediate vicinity of the hair shaft. These glands open through their ducts into the hair root canal, thus forming a common anatomical structure, the pilosebaceous apparatus (PSA). The causes of disturbances in the structure and/or function of the sebaceous glands and/or the PSA leading to or predisposing to acne, are not known. The sex hormones and possibly other hormones may play a role in regulating the sebaceous glands and/or the PSA. Excessive lipids placed on the skin from exogenous sources are an example of a cause which can lead to a condition resembling acne.
The pathological mechanism underlying acne includes a number of steps. Inspissation of sebum at the external orifice of the sebaceous gland duct and/or the hair follicle leads to formation of a "plug" (comedone) which obstructs the flow of sebum. On exposure to oxygen, the comedone turns dark forming what is commonly referred to as a "black head". The water content of the comedone is reduced by evaporation and diffusion into the adjacent horny layer (keratin) of the surface epidermis resulting in a hardening of the comedone, starting at the external surface. The comedone may become attached to the keratin and thus "moored" to adjacent elements of the skin. The comedone becomes modified chemically, as well as physically, thus becoming a material which is foreign to the body. This state of "foreignness" should provoke an inflammatory reaction, including immune reactions and other responses of various defense systems, particularly those associated with granulocytes and macrophages. If the inflammatory reaction and the immune and other defense responses are effective in eliminating or containing the effects of the comedone, further progression of acne manifestations do not occur. Frequently, however, the immune and other defense reactions are not effective in terminating the acne process at this stage and the process progresses partly or wholly as described below.
While the comedone is obstructing the outlet of the duct, the sebaceous glands can continue to form sebum, which accumulates in the duct and in the glands, distending both. The distension and the resulting pressure lead to further intensification of the inflammatory reaction in the adjacent skin and subcutaneous tissues and produce additional swelling (edema), redness (erythema), discomfort, and a mass, which includes the obstructed and thefore encysted sebaceous gland ("redhead", "pimple", or acne papule). Frequently, the defense mechanisms are not adequate to terminate this process promptly at the acne papule stage and it continues to progress as outlined below.
The above conditions favor the growth of bacteria, and the resultant infections involve the duct, the sebaceous glands and the surrounding tissues, usually in that order. The onset of the infection produces further inflammatory changes, thereby initiating a vicious cycle causing continued and/or increased obstruction of the outflow of the sebum, which in turn leads to more pressure, more inflammation and continued or progressive infection. This leads to the formation of the acne pustule. The immune and other defense mechanisms having been inadequate to prevent these conditions from arising, frequently fail to arrest or reverse the process early in the acne pustule stage and it persists or progresses further.
Obstruction with or without infection leads to the formation of cysts. Infection of a cyst results in the formation of an abscess which leads to local tissue destruction. If this destruction of tissue has involved the connective tissue elements of the skin or subcutaneous tissues to a sufficient degree, healing is frequently accompanied and/or followed by scar formation.
The scars in acne can vary from minimal to extensive and severely disfiguring problems which are permanent sequallae of acne. While the process by which acne arises and lasts for an indefinite time may and frequently does come to a halt as a result of treatment or spontaneously, the scars persist for life unless they are removed, usually by a surgical method.
While there are many treatment methods which have been used, it is generally agreed that there is no uniformly satisfactory method for curing or even controlling acne. The therapeutic methods which are available, address themselves primarily to the palliative management of the manifestations of acne, (resulting from the abnormalities of the sebum and the sebaceous glands) such as oiliness, comedones, infections and scars. Representative of but a few of the many methods and compositions proposed heretofor for the treatment of acne, reference is made to U.S. Pat. Nos. 3,535,422; 3,663,716; 3,671,643; 3,867,522 and 3,886,278.
Accordingly, it is the primary object of the present invention to provide a treatment for and therapeutic control of acne.
This and other objects of the present invention will become more apparent from the discussion which follows.